Assessing the safety and effectiveness of ENV-501 in patients with HER3-expressing solid tumors

A First-in-Human, Open-label, Phase 1/2 Clinical Trial to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMBD-501 in Patients With Advanced-Stage, Relapsed/Refractory HER3-Expressing Solid Tumors

This study is testing a new treatment called ENV-501 to see if it is safe and effective for people with advanced solid tumors that express HER3, like melanoma, lung cancer, and breast cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hummingbird Bioscience (Industry-sponsored)
• Drugs / interventions: Radiation
• Locations: 7 sites (La Jolla, California and 6 other locations)
• Trial ID: NCT06956690 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 clinical trial evaluates ENV-501, a treatment for patients with advanced-stage HER3-expressing solid tumors, including melanoma, non-small cell lung cancer, and breast cancer. The trial consists of two phases: the first phase focuses on determining the safety and tolerability of escalating doses of ENV-501, while the second phase aims to assess its preliminary efficacy in a larger patient cohort. Patients will receive doses of ENV-501 based on the results from the initial phase to identify the optimal dosing schedule for further evaluation.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced-stage or metastatic HER3+ solid tumors who are relapsed, refractory, or ineligible for standard therapy.

Not a fit: Patients with HER3-negative tumors or those who have not exhausted standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced HER3-expressing solid tumors that have not responded to standard therapies.

How similar studies have performed: While this approach is novel in targeting HER3-expressing tumors, similar studies targeting other HER receptors have shown promise in the past.

Eligibility criteria

Inclusion Criteria:

* Body weight ≥ 40 kg.
* Willing and able to provide signed written informed consent before any study-related screening procedures are performed.
* Patients with histologically or cytologically confirmed diagnosis of advanced-stage or metastatic HER3+ solid tumors that are relapsed or refractory to or ineligible for standard therapy, or for whom no standard therapy is available; or the patient has documented their refusal of standard of care therapies. These include the following:

  1. Unresectable or metastatic cutaneous melanoma (HER3+)
  2. Locally advanced or metastatic mutated EGFR (mEGFR) NSCLC (HER3+)
  3. Unresectable, locally advanced or metastatic breast cancer
  4. Relapsed or refractory solid tumors, with documented HER3+ expression such as Pancreatic Ductal Adenocarcinoma (PDAC) and gastric cancers, may be allowed in the protocol following sponsor approval on a case-by -case basis.
* If molecular pathology report to confirm HER3+ status is not available, willingness to undergo fresh tumor biopsy for retrospective assessment of HER3+ status following enrollment..
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
* Contraceptive requirements:

  1. Women of childbearing potential (WOCBP) must use contraception from at least 28 days prior to study start, during the study, and for at least 6 months after the last dose of study drug.
  2. Males who are sexually active with partner(s) who are WOCBP must agree to use a male condom with spermicide beginning at study start, during the study and for at least 6 months after the last dose of study drug.
* Females must:

  1. Agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study drug.
  2. Agree to not breastfeed and do not plan to become pregnant during the study and for at least 6 months after the last dose of study drug.
* Males must:

  1. Agree to not donate sperm beginning at study start, during the study, and for at least 6 months after the last dose of study drug.
  2. Agree to not plan to father a child beginning at study start, during the study, and for at least 6 months after last dose of study drug.
* Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

* Any of the following treatment interventions within the specified time frame prior to study drug administration at study start:

  1. Any anti-tumor-directed drug therapy within 21 days or 5 times the elimination half-life (whichever is shorter).
  2. Treatment with investigational drugs within 21 days.
  3. Major surgery within 21 days.
  4. Radiation therapy ≤4 weeks or radiotherapy that included \>30% of the bone marrow.
  5. Autologous or allogeneic stem cell transplantation or allogeneic tissue/organ transplant within 3 months.
  6. CYP3A4 strong inhibitor (including any prescription or non-prescription drugs or herbal supplements) ≤4 half-lives.
  7. CYP3A4 strong inducer ≤4 half-lives.
  8. OATP1B inhibitor (including any prescription or non-prescription drugs or herbal supplements) ≤4 half-lives.
* Prior treatment with a HER3-targeted ADC or any exatecan- or exatecan-derivative-conjugated ADC inhibitor as last line of therapy.
* Prior treatment with a topoisomerase I inhibitor as last line of therapy.
* Primary immune deficiency (e.g. congenital syndromes).
* Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment within 2 weeks prior to study start.
* Known/suspected hypersensitivity against ENV-501, human or humanized immunoglobulin Gs (IgGs), or their ingredients.
* History of noninfectious or drug-induced pneumonitis or interstitial lung disease (ILD).
* Known seropositivity (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
* Leptomeningeal disease, symptomatic or uncontrolled (active) brain metastasis (note: brain metastases not requiring steroids or anti-epileptic therapy are allowed if stable for ≥4 weeks prior to study start and patient is neurologically stable).
* Pregnant or WOCBP who have a positive b-human chorionic gonadotropin (HCG) test result at Screening or within 7 days prior to study start.
* Patients with second malignancies that are active (uncontrolled, metastatic) or requiring therapy.
* Patient who is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study site or the Sponsor.

Where this trial is running

La Jolla, California and 6 other locations

• Research Site — La Jolla, California, United States (Recruiting)
• Research Site — Indianapolis, Indiana, United States (Recruiting)
• Research Site — Farmington Hills, Michigan, United States (Recruiting)
• Research Site — Dallas, Texas, United States (Recruiting)
• Research Site — San Antonio, Texas, United States (Recruiting)
• Research Site — Campbelltown, New South Wales, Australia (Withdrawn)
• Research Site — Miranda, New South Wales, Australia (Withdrawn)

Study contacts

• Study coordinator: Kevin Heller, Dr

Conditions Melanoma; Non Small Cell Lung Cancer; Breast Cancer